Who is the manufacturer of ISE Electrodes?

Randox Laboratories, Ltd. filed the 510(k) submission for ISE Electrodes (K230890).

What is the FDA product code for ISE Electrodes?

CEM. It is classified under 21 CFR 862.1600 as a Class 2 device in the Clinical Chemistry panel.

What is the regulatory pathway for ISE Electrodes?

510(k) clearance (submission type: Special).

Who can help prepare an FDA 510(k) submission like ISE Electrodes?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

ISE Electrodes

K230890 · Randox Laboratories, Ltd. · CEM · Sep 8, 2023 · Clinical Chemistry

Device Facts

Record ID	K230890
Device Name	ISE Electrodes
Applicant	Randox Laboratories, Ltd.
Product Code	CEM · Clinical Chemistry
Decision Date	Sep 8, 2023
Decision	SESE
Submission Type	Special
Regulation	21 CFR 862.1600
Device Class	Class 2

Intended Use

The ISE Electrodes on the RX Imola can be used for measurement of the electrolytes sodium, potassium and chloride in serum and urine and for use in diagnosis and treatment of electrolyte imbalance. For in vitro diagnostic use only.

Device Story

The ISE Electrodes are an Ion Selective Electrode module for the RX imola automated clinical chemistry analyzer. The system uses direct potentiometry to measure sodium, potassium, and chloride concentrations in serum and urine samples. The analyzer uses a barcode system for sample identification and interacts with a host computer for test selection. The module replaces a discontinued unit; it utilizes specific electrodes and calibration solutions (L-solution, H-solution) to perform quantitative analysis. The device is intended for use in clinical laboratory settings by trained personnel. Output is provided as electrolyte concentration values, which clinicians use to diagnose and manage electrolyte imbalances, potentially improving patient outcomes through accurate monitoring.

Clinical Evidence

Bench testing only; no clinical data provided. Substantial equivalence supported by design control activities, risk analysis, and verification/validation of the modified ISE module.

Technological Characteristics

Ion-selective electrode (ISE) technology for electrolyte measurement. Components include electrodes for potassium, chloride, and sodium. Modification pertains to the ISE module assembly. System is intended for use with the RX Imola clinical chemistry analyzer.

Indications for Use

Indicated for the measurement of sodium, potassium, and chloride electrolytes in serum and urine to aid in the diagnosis and treatment of electrolyte imbalance in patients.

Regulatory Classification

Identification

A potassium test system is a device intended to measure potassium in serum, plasma, and urine. Measurements obtained by this device are used to monitor electrolyte balance in the diagnosis and treatment of diseases conditions characterized by low or high blood potassium levels.

Predicate Devices

RX imola (K052914)

Related Devices

K070531 — ISE MODULE AND BAR CODE READER ADDITION FOR THE DATAPRO CLINICAL CHEMISTRY ANALYZER · Thermo Fisher Scientific · Sep 4, 2007
K053165 — ISE INDIRECT NA, K, CL FOR GEN.2 · Roche Diagnostics Corp. · Dec 14, 2005
K123726 — COBAS 8000 ISE INDIRECT NA, K, CI FOR GEN. 2 · Roche Diagnostics · May 21, 2013
K102959 — PROLYTE ELECTROLYTE ANALYZER · Diamond Diagnostics, Inc. · Jan 14, 2011

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG ADMINISTRATION" in blue as well. The FDA is a federal agency responsible for regulating and supervising the safety of food, drugs, and other products. September 8, 2023 Randox Laboratories Limited Karena Shaw Regulatory Affairs Manager 55 Diamond Road County Antrim, BT29 40Y United Kingdom #### Re: K230890 Trade/Device Name: ISE Electrodes Regulation Number: 21 CFR 862.1600 Regulation Name: Potassium Test System Regulatory Class: Class II Product Code: CEM, CGZ, JGS Dated: August 11, 2023 Received: August 11, 2023 #### Dear Karena Shaw: We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part {1}------------------------------------------------ 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems. For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100). Sincerely, Paula V. Caposino -S Paula Caposino, Ph.D. Acting Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Ouality Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ # Indications for Use 510(k) Number (if known) K230890 Device Name ISE Electrodes Indications for Use (Describe) The ISE Electrodes on the RX Imola can be used for measurement of the electrolytes sodium, potassium and chloride in serum and urine and for use in diagnosis and treatment of electrolyte imbalance. For in vitro diagnostic use only. | Type of Use (Select one or both, as applicable) | | |------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------| | <div style="display:flex; align-items:center;">☒Prescription Use (Part 21 CFR 801 Subpart D)</div> | <div style="display:flex; align-items:center;">☐Over-The-Counter Use (21 CFR 801 Subpart C)</div> | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ Image /page/3/Picture/1 description: The image shows the word "RANDOX" in green letters. The "O" in the word is replaced with a red circle. The letters are bold and sans-serif. # SPECIAL 510(k) SUMMARY K230890 #### General Information Name: Randox Laboratories Limited 55 Diamond Road, Crumlin, Address: County Antrim, BT29 4QY, United Kingdom. > Telephone: +44 (0) 28 9442 2413 Fax: +44 (0) 28 9445 2912 Contact: Karena Shaw E-mail: karena.shaw@randox.com #### Device Identification #### Proprietary Names: ISE Electrodes #### Table 1: Candidate Device Regulatory Summary | Product Code | Regulation Name | Classification | Regulation Section | Panel | |-----------------|---------------------------------------|----------------|--------------------|----------------------------| | CEM | Electrode, Ion-Specific, Potassium | II | 21 CFR 862.1600 | Clinical Chemistry (75) | | CGZ | Electrode, Ion-Specific, Chloride | II | 21 CFR 862.1170 | Clinical Chemistry (75) | | JGS | Electrode, Ion-Specific, Sodium | II | 21 CFR 862.1665 | Clinical Chemistry (75) | #### Predicate Device: Previously cleared unmodified device: RX imola (k052914) {4}------------------------------------------------ Image /page/4/Picture/1 description: The image shows the word "RANDO" in green, with a red circle in the middle of the "O". The font is bold and sans-serif. The background is white. # DEVICE DESCRIPTION RX imola is an automated clinical chemistry analyzer complete with dedicated analyzer software. Software functions of the analyzer include the facility to interact with a host computer for direct download of test method selection details for individual samples. A barcode system is used for the rapid identification of patient samples, reagents and QC samples, In addition, the RX imola is fitted with an Ion Selective Electrode (ISE) module that operates in conjunction with specific electrodes for the quantitative in vitro diagnostic determination of Sodium, Potassium and Chloride in serum and urine. #### INTENDED USE The ISE Electrodes on the RX Imola can be used for measurement of the electrolytes sodium, potassium and chloride in serum and urine and for use in diagnosis and treatment of electrolyte imbalance. For in vitro diagnostic use only. # DESCRIPTION OF MODIFICATION TO EXISTING DEVICE Following discontinuation of the original ISE unit, the RX imola instruments purchased will now be fitted with a new ISE electrodes for Sodium, Potassium & Chlorides. RX imola instruments fitted with the new ISE electrodes will be identified by an alternate serial number prefix (7255). The new ISE unit being implemented through this Special 510(k) was previously cleared under k131554 for our RX DAYTONA PLUS CHEMISTRY ANALYZER. The data included in this Special 510(k) summary is based on a comparison of the original ISE electrodes used in conjunction with RX imola (K052914) and the new ISE electrodes that will now be used with the RX imola. # COMPARISON WITH PREDICATE DEVICE The following table describes the similarities and differences between - ISE device originally cleared with the RX imola through K052914 . - Candidate ISE device with the RX imola analyser ● # Table 2: Comparison with predicate device Similarities {5}------------------------------------------------ Image /page/5/Picture/1 description: The image shows the word "RANDOX" in green letters. The "O" in the word is a red circle. The letters are bold and sans-serif. | Parameter | RX imola Automated Analyzer With previous ISE unit (ORIGINALLY CLEARED DEVICE K052914) | RX imola Automated Analyzer With New ISE Unit (CANDIDATE DEVICE K230890) | |------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------| | Intended Use | Used for measurement of the electrolytes sodium, potassium and chloride in serum and urine for diagnosis and treatment of electrolyte imbalance | Used for measurement of the electrolytes sodium, potassium and chloride in serum and urine for diagnosis and treatment of electrolyte imbalance | | Method | Direct | Direct | | Calibration Frequency | 8 Hours | 8 Hours | | ISE Electrodes Usage [10 000 Samples] | REF: 360 Days Na+: 360 Days K+: 180 Days Cl-: 90 Days | REF: 360 Days Na+: 360 Days K+: 180 Days Cl-: 90 Days | | ISE Sample Types | Serum Urine | Serum Urine | | Environmental Operating Temperature | 15°C to 30°C | 15°C to 30°C | | Parameter | RX imola Automated Analyzer With previous ISE unit (ORIGINALLY CLEARED DEVICE K052914) | RX imola Automated Analyzer With New ISE Unit (CANDIDATE DEVICE K230890) | | ISE Throughput | 240 tests per hour | 180 tests per hour | | Consumables | Medica: Reference Electrode | Horiba: Reference Electrode | | | Medica: Sodium Electrode (Na+) | Horiba: Sodium Electrode (Na+) | | | Medica: Potassium (K+) | Horiba: Potassium (K+) | | | Medica: Chloride (Cl-) | Horiba: Chloride (Cl-) | | | Medica: CAL A | Horiba: L-Solution | | | Medica: CAL B (Calibrator) | Horiba: H-Solution (Calibrator) | | | Medica: Clean Solution | Horiba: Clean Solution | | | Medica: Urine Diluent (for urine ISE) | Horiba: Urine Diluent (for urine ISE) | | | | Horiba: Etching Solution | | | | Horiba: Ref-Solution | | Sample Volume | 70ul | 53ul | | Calibration Type | 2-Point (CAL A + CAL B) | 2-Point (L-solution + H-Solution) | | Analysis Time | Serum - 30s including 1-point calibration Urine - 60s including 1-point calibration | Serum - 36s including 1 point calibration Urine - 54s including 1 point calibration | | ISE Module Size | 100mm (H) x 102mm (W) x 91 mm (D) | 175mm (H) x 205mm (W) x 95 mm (D) | | Maximum Environmental Temperature (Unopened Storage) | 38°C | 45°C | | Calibration Pass Range | Na+ pass range (50 mV - 66 mV) | Na+ pass range (38 mV - 65 mV) | | | K+ pass range (50 mV - 63 mV) | K+ pass range (37 mV - 67mV) | | | Cl- pass range (40 mV - 59 mV) | Cl- pass range (28 mV - 53 mV) | Differences {6}------------------------------------------------ Image /page/6/Picture/1 description: The image shows the word "RANDOX" in green letters. The "O" in the word is a red circle. The letters are bold and sans-serif. The word is centered in the image. {7}------------------------------------------------ Image /page/7/Picture/1 description: The image shows the word "RANDOX" in green letters. The "O" in the word is a red circle. The font is bold and sans-serif. #### ANALYTICAL PERFORMANCE: #### Precision/Reproducibility: Precision was evaluated consistent with C.L.S.I document EP05-A3 'Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline- Third Edition.' Serum precision studies were performed on two RX imola systems using two levels of control material and at least five human serum samples for Sodium, Potassium and Chloride. Urine precision studies were performed on the same two RX imola systems for Sodium, Potassium and Chloride using two levels of urine controls and at least five urine patient pools. Testing was conducted twice per day for 20 non-consecutive days. Two replicates per run was performed for each sample. The results are summarized in the tables below: #### Table 3: Sodium Serum Precision Summary | | Control 1 | Control 2 | Serum Pool 1 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | Serum Pool 6 | |---------------|-----------|-----------|--------------|--------------|--------------|--------------|--------------|--------------| | Mean (mmol/l) | 143.72 | 160.93 | 101.68 | 111.00 | 118.67 | 136.38 | 162.38 | 192.10 | | SD | 0.88 | 1.01 | 0.69 | 0.59 | 1.88 | 0.47 | 2.69 | 0.37 | | CV (%) | 0.6 | 0.6 | 0.7 | 0.5 | 1.6 | 0.3 | 1.7 | 0.2 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | #### Within run precision #### Total precision | | Control 1 | Control 2 | Serum Pool 1 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | Serum Pool 6 | |---------------|-----------|-----------|--------------|--------------|--------------|--------------|--------------|--------------| | Mean (mmol/l) | 143.72 | 160.93 | 101.68 | 111.00 | 118.67 | 136.38 | 162.38 | 192.10 | | SD | 1.57 | 2.17 | 2.11 | 1.39 | 2.37 | 1.63 | 3.61 | 3.71 | | CV (%) | 1.1 | 1.4 | 2.1 | 1.3 | 2.0 | 1.2 | 2.2 | 1.9 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | {8}------------------------------------------------ Image /page/8/Picture/1 description: The image shows the word "RANDO" in green letters. The letter "O" is replaced with a red circle. The font is bold and sans-serif. The background is white. # Table 4: Potassium Serum Precision Summary # Within run precision | | Control 1 | Control 2 | Serum Pool 1 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | Serum Pool 6 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 4.00 | 6.43 | 0.91 | 2.16 | 3.26 | 4.56 | 6.58 | 9.73 | | SD | 0.02 | 0.04 | 0.02 | 0.01 | 0.01 | 0.03 | 0.04 | 0.05 | | CV (%) | 0.6 | 0.7 | 1.9 | 0.4 | 0.4 | 0.8 | 0.6 | 0.5 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | # Total precision | | Control 1 | Control 2 | Serum Pool 1 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | Serum Pool 6 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 4.00 | 6.43 | 0.91 | 2.16 | 3.26 | 4.56 | 6.58 | 9.73 | | SD | 0.04 | 0.09 | 0.04 | 0.04 | 0.04 | 0.06 | 0.09 | 0.20 | | CV (%) | 0.9 | 1.4 | 4.1 | 1.6 | 1.3 | 1.2 | 1.4 | 2.1 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | # Table 5: Chloride Serum Precision Summary #### Within run precision | | Control 1 | Control 2 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 98.27 | 120.99 | 83.30 | 96.14 | 117.38 | 161.10 | | SD | 0.68 | 0.95 | 0.79 | 0.94 | 0.50 | 0.74 | | CV (%) | 0.7 | 0.8 | 1.0 | 1.0 | 0.4 | 0.5 | | n | 80 | 80 | 80 | 80 | 80 | 80 | # Total precision | | Control 1 | Control 2 | Serum Pool 2 | Serum Pool 3 | Serum Pool 4 | Serum Pool 5 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 98.27 | 120.99 | 83.30 | 96.14 | 117.38 | 161.10 | | SD | 1.04 | 1.54 | 1.85 | 1.02 | 1.06 | 3.55 | | CV (%) | 1.1 | 1.3 | 2.2 | 1.1 | 0.9 | 2.2 | | n | 80 | 80 | 80 | 80 | 80 | 80 | {9}------------------------------------------------ Image /page/9/Picture/1 description: The image shows the word "RANDO" in green letters. There is a red dot in the middle of the letter "O". The letters are bold and sans-serif. The background is white. # Table 6: Sodium Urine Precision Summary # Within run precision | | Control 1 | Control 2 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | Urine Pool 6 | |---------------|-----------|-----------|--------------|--------------|--------------|--------------|--------------| | Mean (mmol/l) | 65.45 | 215.33 | 84.72 | 118.01 | 179.59 | 257.99 | 285.71 | | SD | 2.48 | 2.83 | 1.91 | 2.41 | 3.08 | 2.88 | 2.77 | | CV (%) | 3.8 | 1.3 | 2.3 | 2.0 | 1.7 | 1.1 | 1.0 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | # Total precision | | Control 1 | Control 2 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | Urine Pool 6 | |---------------|-----------|-----------|--------------|--------------|--------------|--------------|--------------| | Mean (mmol/l) | 65.45 | 215.33 | 84.72 | 118.01 | 179.59 | 257.99 | 285.71 | | SD | 3.85 | 8.94 | 3.18 | 3.19 | 4.71 | 6.11 | 7.16 | | CV (%) | 5.9 | 4.2 | 3.8 | 2.7 | 2.6 | 2.4 | 2.5 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | # Table 7: Potassium Urine Precision Summary # Within run precision | | Control 1 | Control 2 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 34.49 | 144.18 | 33.54 | 85.89 | 122.59 | 160.81 | | SD | 0.32 | 0.93 | 0.21 | 0.82 | 0.77 | 1.73 | | CV (%) | 0.9 | 0.6 | 0.6 | 1.0 | 0.6 | 1.1 | | n | 80 | 80 | 80 | 80 | 80 | 80 | #### Total precision | | Control 1 | Control 2 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 34.49 | 144.18 | 33.54 | 85.89 | 122.59 | 160.81 | | SD | 0.77 | 4.80 | 0.73 | 2.49 | 4.10 | 6.50 | | CV (%) | 2.2 | 3.3 | 2.2 | 2.9 | 3.3 | 4.0 | | n | 80 | 80 | 80 | 80 | 80 | 80 | {10}------------------------------------------------ Image /page/10/Picture/1 description: The image shows the word "RANDO" in green letters. The letter "O" has a red dot in the center. The font is bold and sans-serif. #### Table 8: Chloride Urine Precision Summary # Within run precision | | Control 1 | Control 2 | Urine Pool 1 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | Urine Pool 6 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 86.04 | 280.01 | 85.63 | 93.06 | 146.38 | 198.19 | 247.72 | 315.40 | | SD | 2.28 | 2.68 | 1.91 | 2.13 | 2.19 | 2.41 | 2.69 | 4.24 | | CV (%) | 2.7 | 1.0 | 2.2 | 2.3 | 1.5 | 1.2 | 1.1 | 1.3 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | # Total precision | | Control 1 | Control 2 | Urine Pool 1 | Urine Pool 2 | Urine Pool 3 | Urine Pool 4 | Urine Pool 5 | Urine Pool 6 | |---------------|--------------|--------------|-----------------|-----------------|-----------------|-----------------|-----------------|-----------------| | Mean (mmol/l) | 86.04 | 280.01 | 85.63 | 93.06 | 146.38 | 198.19 | 247.72 | 315.40 | | SD | 2.93 | 7.57 | 2.97 | 3.33 | 3.67 | 4.53 | 7.66 | 8.12 | | CV (%) | 3.4 | 2.7 | 3.5 | 3.6 | 2.5 | 2.3 | 3.1 | 2.6 | | n | 80 | 80 | 80 | 80 | 80 | 80 | 80 | 80 | # Precision Conclusion The acceptance criteria for precision was met for serum and urine for all analytes (Sodium, Potassium and Chloride) on the RX imola with the modified ISE device. {11}------------------------------------------------ Image /page/11/Picture/1 description: The image shows the word "RANDOX" in a bold, sans-serif font. The letters are a dark teal color, except for the "O", which has a red circle in the center. The logo is simple and modern, with a focus on the company name. #### Linearity/assay reportable range: Linearity studies have been carried out in serum and urine in accordance with C.L.S.I. standard EP6-A 'Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline'. Linearity studies were performed at 9 levels to determine the analytical range of an assay - that is the range where the reported result is a linear function to the analyte concentration (or where deviation from linearity is less than 5%). The linearity samples were prepared at 9 levels to cover the measuring intervals in the table below. | Analyte | Specimen Type | Measuring Interval (mmol/L) | |-----------|---------------|-----------------------------| | Sodium | Serum | 90 to 200 | | | Urine | 45 to 318 | | Potassium | Serum | 0.5 to 11 | | | Urine | 7 to 168 | | Chloride | Serum | 72 to 210 | | | Urine | 61 to 319 | #### Table 9: Linearity Results Summary # Linearity Conclusion The results of the linearity studies support the above claimed measuring ranges for serum and urine for all analytes (Sodium, Potassium and Chloride) on the RX imola with the modified ISE device. {12}------------------------------------------------ Image /page/12/Picture/1 description: The image shows the word "RANDOX" in green, with the "O" in "RANDOX" being a red circle. The letters are bold and sans-serif. The logo is simple and modern. # Specificity/Interference Evaluation of specificity/interference was carried out in serum and urine in accordance with EP07 3rd Edition 'Interference Testing in Clinical Chemistry.' The analytes below were tested in serum up to the following levels and were found not to interfere with Sodium, Potassium and Chloride determination. ISE Sodium, Potassium and Chloride Interference Summary (in Serum) The analytes below were added to normal serum and found not to interfere up to the following levels. | | Sodium - 130 mmol/l | Potassium - 3 mmol/l | Chloride - 90 mmol/l | |---------------------|---------------------|----------------------|----------------------| | Haemoglobin | 1000 mg/dl | 126 mg/dl | 1000 mg/dl | | Total Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl | | Conjugate Bilirubin | 60 mg/dl | 60 mg/dl | 49.5 mg/dl | | Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | | IntralipidⓇ | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | #### Table 10: Analytes Added to Normal Serum Level 1 #### Table 11: Analytes Added to Normal Serum Level 2 | | Sodium - 150 mmol/l | Potassium - 5 mmol/l | Chloride - 110 mmol/l | |---------------------|---------------------|----------------------|-----------------------| | Haemoglobin | 1000 mg/dl | 205 mg/dl | 1000 mg/dl | | Total Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl | | Conjugate Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl | | Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | | Intralipid® | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | {13}------------------------------------------------ Image /page/13/Picture/1 description: The image shows the word "RANDOX" in green letters. The "O" in the word is replaced with a red circle. The letters are bold and sans-serif. | Interfering Substance | Sodium 130 mmol/l | Potassium 3 mmol/l | Chloride 90 mmol/l | |--------------------------|-------------------|--------------------|--------------------| | Bromide | 37.5 mmol/l | 37.5 mmol/l | 37.5 mmol/l | | Ascorbic Acid | 341 umol/L | 341 umol/L | 341 umol/L | | Thiocyanate | 6.88 mmol/l | 0.8 mmol/l | 1.12 mmol/l | | Lithium | 3.2 mmol/l | 3.2 mmol/l | 3.2 mmol/l | | Salicylic Acid | 4.3 mmol/l | 4.3 mmol/l | 4.3 mmol/l | #### Table 12: Exogenous Interferences in Serum - Level 1 #### Table 13: Exogenous Interferences in Serum - Level 2 | Interfering Substance | Sodium 150 mmol/l | Potassium 5 mmol/l | Chloride 110 mmol/l | |--------------------------|-------------------|--------------------|---------------------| | Bromide | 37.5 mmol/l | 37.5 mmol/l | 37.5 mmol/l | | Ascorbic Acid | 341 µmol/L | 341 µmol/L | 341 µmol/L | | Thiocyanate | 6.88 mmol/l | 0.85 mmol/l | 1.25 mmol/l | | Lithium | 3.2 mmol/l | 3.2 mmol/l | 3.2 mmol/l | | Salicylic Acid | 4.3 mmol/l | 4.3 mmol/l | 4.3 mmol/l | #### ISE Sodium, Potassium and Chloride Urine Interference (in urine) summary The analytes below were added to normal urine and found not to interfere up to the following levels. #### Table 14: Analytes Added to Normal Urine Specificity/Interference Level 1 | | Sodium 40 mmol/l | Potassium 25 mmol/l | Chloride 110 mmol/l | |---------------------|------------------|---------------------|---------------------| | Haemoglobin | 590 mg/dl | 765 mg/dl | 1000 mg/dl | | Total Bilirubin | 17.4 mg/dl | 60 mg/dl | 60 mg/dl | | Conjugate Bilirubin | 22 mg/dl | 60 mg/dl | 44.5 mg/dl | | Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | | Intralipid® | 810 mg/dl | 2000 mg/dl | 2000 mg/dl | {14}------------------------------------------------ Image /page/14/Picture/1 description: The image shows the word "RANDO" in green, with a red circle in place of the letter "O", followed by the letter "X" in green. The font is bold and sans-serif. The logo is likely for a company or organization named Randox. | | Sodium 220 mmol/l | Potassium 125 mmol/l | Chloride 250 mmol/l | |---------------------|-------------------|----------------------|---------------------| | Haemoglobin | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl | | Total Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl | | Conjugate Bilirubin | 60 mg/dl | 60 mg/dl | 60 mg/dl | | Triglycerides | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | | Intralipid® | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | #### Table 15: Analytes Added to Normal Urine Specificity/Interference Level 2 #### Table 16: Exogenous Interferences in Urine - Level 1 | Interfering Substance | Sodium 40 mmol/l | Potassium 25 mmol/l | Chloride 110 mmol/l | |--------------------------|------------------|---------------------|---------------------| | Ascorbic Acid | 200 mg/dl | 200 mg/dl | 200 mg/dl | | Boric Acid | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl | | Ethanol | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl | | Gamma Globulin | 500 mg/dl | 500 mg/dl | 500 mg/dl | | Glucose | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | | HSA | 500 mg/dl | 500 mg/dl | 500 mg/dl | # Table 17: Exogenous Interferences Level 2 (Urine) | Interfering Substance | Sodium 220 mmol/l | Potassium 125 mmol/l | Chloride 250 mmol/l | |--------------------------|-------------------|----------------------|---------------------| | Ascorbic Acid | 200 mg/dl | 200 mg/dl | 200 mg/dl | | Boric Acid | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl | | Ethanol | 1000 mg/dl | 1000 mg/dl | 1000 mg/dl | | Gamma Globulin | 500 mg/dl | 500 mg/dl | 500 mg/dl | | Glucose | 2000 mg/dl | 2000 mg/dl | 2000 mg/dl | | HSA | 500 mg/dl | 500 mg/dl | 500 mg/dl | {15}------------------------------------------------ # Method comparison with predicate device: Correlation studies were carried out for serum and urine in accordance with C.L.S.I. guideline EP09c 'Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline- Third Edition'. A method comparison was conducted against the unmodified device (cleared under k052914) to confirm the device is substantially equivalent. Testing was conducted on two RX imola analysers, one RX imola analyser with the modified device, and the other RX imola analyser with the unmodified device. # Correlation (Serum) # Sodium This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: - Y = 1.06x - 8.4 R = 0.973 105 patient serum samples were analysed spanning the range 111.7 to 195.8 mmol/l. # Potassium This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: - Y = 1.02x - 0.09 R = 0.998 109 patient serum samples were analysed spanning the range 0.96 to 10.63 mmol/l. # Chloride This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: - Y = 1.03x - 6.59 R = 0.987 104 patient serum samples were analysed spanning the range 86.2 to 196.2 mmol/l. {16}------------------------------------------------ Image /page/16/Picture/1 description: The image shows the word "RANDOXX" in green letters. The "O" in "RANDOXX" has a red dot in the center. The letters are bold and sans-serif. # Correlation (Urine) # Sodium This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: - Y = 0.92x + 6.43 R = 0.997 72 patient urine samples were analysed spanning the range 49.4 to 298.6 mmol/l. # Potassium This method – RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: - Y = 1.03x = 1.02 R = 0.999 84 patient urine samples were analysed spanning the range 9.5 to 167.6 mmol/l. # Chloride This method - RX imola new ISE unit (Y) was compared with method on the RX imola with previous ISE unit (X) and the following linear regression equation obtained: - Y = 0.89x + 18.49 R = 0.986 90 patient urine samples were analysed spanning the range 84.8 - 226.8 mmol/l. # DESIGN CONTROL ACTIVITIES The verification and validation of the device modification has been performed under design control. The design control activities were based on the risk analysis and acceptance criteria were set to maintain the performance and safety of the device. The verification and validation includes in-house studies of precision, method comparison, interferences and linearity. {17}------------------------------------------------ Image /page/17/Picture/1 description: The image shows the word "RANDO" in green letters, with a red circle in the middle of the letter "O". The letters are bold and sans-serif. The background is white. #### RISK ANALYSIS A Risk Analysis was performed to identify any new risks associated with the change in the ISE electrodes provided with the RX imola. Based on this and the testing the results indicate that the changes to the ISE unit on the RX imola are safe and effective for the stated intended use and are substantially equivalent to the previously approved device. #### OVERALL CONCLUSION The modified device is substantially equivalent to the unmodified device (cleared under k052914).